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Protein

Fibronectin type III domain-containing protein 5

Gene

FNDC5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Irisin: Contrary to mouse, may not be involved in the beneficial effects of muscular exercise, nor in the induction of browning of human white adipose tissue.1 Publication

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hormone

Enzyme and pathway databases

BioCyciZFISH:ENSG00000160097-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Fibronectin type III domain-containing protein 5
Alternative name(s):
Fibronectin type III repeat-containing protein 2
Cleaved into the following chain:
Gene namesi
Name:FNDC5
Synonyms:FRCP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:20240. FNDC5.

Subcellular locationi

Irisin :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini32 – 152ExtracellularSequence analysisAdd BLAST121
Transmembranei153 – 173HelicalSequence analysisAdd BLAST21
Topological domaini174 – 212CytoplasmicSequence analysisAdd BLAST39

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Peroxisome, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi252995.
OpenTargetsiENSG00000160097.
PharmGKBiPA134924607.

Polymorphism and mutation databases

DMDMi403314395.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31Sequence analysisAdd BLAST31
ChainiPRO_000032897132 – 212Fibronectin type III domain-containing protein 5Add BLAST181
ChainiPRO_000041585732 – 143IrisinAdd BLAST112

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi39N-linked (GlcNAc...)Sequence analysis1
Glycosylationi84N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

The extracellular domain is cleaved and released from the cell membrane.
N-Glycosylated.By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ8NAU1.
PeptideAtlasiQ8NAU1.
PRIDEiQ8NAU1.

PTM databases

iPTMnetiQ8NAU1.
PhosphoSitePlusiQ8NAU1.

Expressioni

Tissue specificityi

Widely expressed, with highest levels in heart. Very low expression, if any, in colon, pancreas and spleen.1 Publication

Inductioni

Has been shown to be up-regulated some twofold by muscular exercise at the mRNA and protein level; this effect has been suggested to be mediated by PPARGC1A (PubMed:22237023). However, up-regulation upon exercise could not be reproduced, at least not at the mRNA level (PubMed:24040023).2 Publications

Gene expression databases

BgeeiENSG00000160097.
CleanExiHS_FNDC5.
ExpressionAtlasiQ8NAU1. baseline and differential.

Organism-specific databases

HPAiHPA051290.

Interactioni

Protein-protein interaction databases

BioGridi128948. 8 interactors.
STRINGi9606.ENSP00000362570.

Structurei

Secondary structure

1212
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi38 – 44Combined sources7
Beta strandi50 – 55Combined sources6
Turni59 – 61Combined sources3
Beta strandi62 – 73Combined sources12
Beta strandi77 – 84Combined sources8
Beta strandi89 – 92Combined sources4
Beta strandi100 – 111Combined sources12
Beta strandi120 – 123Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4LSDX-ray2.28A/B/C/D/E/F/G/H33-130[»]
ProteinModelPortaliQ8NAU1.
SMRiQ8NAU1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini36 – 127Fibronectin type-IIIPROSITE-ProRule annotationAdd BLAST92

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi210 – 212Microbody targeting signalSequence analysis3

Sequence similaritiesi

Contains 1 fibronectin type-III domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IESX. Eukaryota.
ENOG410YC2F. LUCA.
GeneTreeiENSGT00390000004923.
HOGENOMiHOG000082536.
HOVERGENiHBG067308.
InParanoidiQ8NAU1.
TreeFamiTF325415.

Family and domain databases

CDDicd00063. FN3. 1 hit.
Gene3Di2.60.40.10. 1 hit.
InterProiIPR003961. FN3_dom.
IPR032073. FNDC5_C.
IPR013783. Ig-like_fold.
[Graphical view]
PfamiPF16066. DUF4808. 1 hit.
PF00041. fn3. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 1 hit.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 1 hit.
PROSITEiPS50853. FN3. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8NAU1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MHPGSPSAWP PRARAALRLW LGCVCFALVQ ADSPSAPVNV TVRHLKANSA
60 70 80 90 100
VVSWDVLEDE VVIGFAISQQ KKDVRMLRFI QEVNTTTRSC ALWDLEEDTE
110 120 130 140 150
YIVHVQAISI QGQSPASEPV LFKTPREAEK MASKNKDEVT MKEMGRNQQL
160 170 180 190 200
RTGEVLIIVV VLFMWAGVIA LFCRQYDIIK DNEPNNNKEK TKSASETSTP
210
EHQGGGLLRS KI
Length:212
Mass (Da):23,659
Last modified:September 5, 2012 - v3
Checksum:iC4A066452A05A134
GO
Isoform 2 (identifier: Q8NAU1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     180-181: KD → EA
     182-212: Missing.

Note: No experimental confirmation available.
Show »
Length:181
Mass (Da):20,281
Checksum:i36BEE521AFABE5A6
GO
Isoform 3 (identifier: Q8NAU1-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-75: Missing.
     212-212: I → VRARPGPGWATLCLMLW

Note: No experimental confirmation available.
Show »
Length:153
Mass (Da):17,323
Checksum:i4DA2ABEAC5B4D934
GO
Isoform 4 (identifier: Q8NAU1-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-75: Missing.

Note: No experimental confirmation available.
Show »
Length:137
Mass (Da):15,527
Checksum:i1045BF9CE29A41E4
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0328601 – 75Missing in isoform 3 and isoform 4. 2 PublicationsAdd BLAST75
Alternative sequenceiVSP_032861180 – 181KD → EA in isoform 2. 1 Publication2
Alternative sequenceiVSP_032862182 – 212Missing in isoform 2. 1 PublicationAdd BLAST31
Alternative sequenceiVSP_032863212I → VRARPGPGWATLCLMLW in isoform 3. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK092102 mRNA. Translation: BAC03806.1.
AC114493 Genomic DNA. No translation available.
CH471059 Genomic DNA. Translation: EAX07499.1.
CH471059 Genomic DNA. Translation: EAX07502.1.
CH471059 Genomic DNA. Translation: EAX07500.1.
BC062297 mRNA. Translation: AAH62297.1.
BX537781 mRNA. Translation: CAD97840.1.
BF221649 mRNA. No translation available.
CCDSiCCDS369.2. [Q8NAU1-1]
CCDS65483.1. [Q8NAU1-3]
RefSeqiNP_001165411.2. NM_001171940.1. [Q8NAU1-2]
NP_001165412.1. NM_001171941.2. [Q8NAU1-3]
NP_715637.2. NM_153756.2. [Q8NAU1-1]
UniGeneiHs.524234.

Genome annotation databases

EnsembliENST00000496770; ENSP00000476320; ENSG00000160097. [Q8NAU1-3]
GeneIDi252995.
KEGGihsa:252995.
UCSCiuc001bwg.5. human. [Q8NAU1-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK092102 mRNA. Translation: BAC03806.1.
AC114493 Genomic DNA. No translation available.
CH471059 Genomic DNA. Translation: EAX07499.1.
CH471059 Genomic DNA. Translation: EAX07502.1.
CH471059 Genomic DNA. Translation: EAX07500.1.
BC062297 mRNA. Translation: AAH62297.1.
BX537781 mRNA. Translation: CAD97840.1.
BF221649 mRNA. No translation available.
CCDSiCCDS369.2. [Q8NAU1-1]
CCDS65483.1. [Q8NAU1-3]
RefSeqiNP_001165411.2. NM_001171940.1. [Q8NAU1-2]
NP_001165412.1. NM_001171941.2. [Q8NAU1-3]
NP_715637.2. NM_153756.2. [Q8NAU1-1]
UniGeneiHs.524234.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4LSDX-ray2.28A/B/C/D/E/F/G/H33-130[»]
ProteinModelPortaliQ8NAU1.
SMRiQ8NAU1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128948. 8 interactors.
STRINGi9606.ENSP00000362570.

PTM databases

iPTMnetiQ8NAU1.
PhosphoSitePlusiQ8NAU1.

Polymorphism and mutation databases

DMDMi403314395.

Proteomic databases

PaxDbiQ8NAU1.
PeptideAtlasiQ8NAU1.
PRIDEiQ8NAU1.

Protocols and materials databases

DNASUi252995.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000496770; ENSP00000476320; ENSG00000160097. [Q8NAU1-3]
GeneIDi252995.
KEGGihsa:252995.
UCSCiuc001bwg.5. human. [Q8NAU1-1]

Organism-specific databases

CTDi252995.
DisGeNETi252995.
GeneCardsiFNDC5.
HGNCiHGNC:20240. FNDC5.
HPAiHPA051290.
MIMi611906. gene.
neXtProtiNX_Q8NAU1.
OpenTargetsiENSG00000160097.
PharmGKBiPA134924607.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IESX. Eukaryota.
ENOG410YC2F. LUCA.
GeneTreeiENSGT00390000004923.
HOGENOMiHOG000082536.
HOVERGENiHBG067308.
InParanoidiQ8NAU1.
TreeFamiTF325415.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000160097-MONOMER.

Miscellaneous databases

ChiTaRSiFNDC5. human.
GenomeRNAii252995.
PROiQ8NAU1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000160097.
CleanExiHS_FNDC5.
ExpressionAtlasiQ8NAU1. baseline and differential.

Family and domain databases

CDDicd00063. FN3. 1 hit.
Gene3Di2.60.40.10. 1 hit.
InterProiIPR003961. FN3_dom.
IPR032073. FNDC5_C.
IPR013783. Ig-like_fold.
[Graphical view]
PfamiPF16066. DUF4808. 1 hit.
PF00041. fn3. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 1 hit.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 1 hit.
PROSITEiPS50853. FN3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFNDC5_HUMAN
AccessioniPrimary (citable) accession number: Q8NAU1
Secondary accession number(s): A6NMC9
, D3DPQ6, Q6P6D9, Q7Z676
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 8, 2008
Last sequence update: September 5, 2012
Last modified: November 30, 2016
This is version 123 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

It is uncertain whether Met-1 or Met-76 is the initiator. Transcript evidence available at present time points at Met-76. In this short version of the protein, the signal peptide cannot be predicted and the irisin peptide is severely truncated. The first initiation codon corresponds to a non-AUG site, an N-terminal ATA codon. This initiation codon has been annotated as it is in good Kozak context and it is conserved in other primates, including gibbon, chimpanzee and gorilla. Although the existence of such a form has not been demonstrated in human, western blot analysis following endurance exercise shows the presence of an irisin peptide of similar size in human and mouse plasma (PubMed:22237023), suggesting the existence of full length irisin in human, at least in some tissues. However, expression from Met-1 may be less efficient than that from Met-76 (PubMed:24040023).2 Publications

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.